Bansal, A

Goepfert, PA

Heath, SL

Jiyu, J

Sabbaj, S

Shacka, JJ

Retrovirology

English

PubMed

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BioMed Central
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Retrovirology
Open AccessPoster presentation
P16-25. HIV specific CTL from elite controllers have a unique 
survival advantage
SL Heath*, J Jiyu, A Bansal, S Sabbaj, JJ Shacka and PA Goepfert
Address: Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
* Corresponding author    
Background
Understanding how elite controllers (EC), patients con-
trolling virus without antiretroviral therapy (ART), differ
from those with chronic disease is an area of intense inves-
tigation. HIV Gag specific (sp) cytotoxic T lymphocytes
(CTL) play a dominant role in this control. Unfortunately,
most HIV sp CTL are primed for apoptosis. We hypothe-
size that EC up-regulate survival factors allowing them to
resist apoptosis.
Methods
We examined pro- and anti-apoptotic factors in HIV Gag
specific CTL in EC (viral load (VL) < 50 off ART), success-
fully treated (ST) (VL < 50 on ART), and untreated virem-
ics (V). Using flow cytometry based assays, we performed
cross-sectional and longitudinal analysis of pro-apoptotic
(cleaved caspase-3) vs. anti-apoptotic (Bcl-2) markers in
HIV specific CD8 T cells examining spontaneous cell
death.
Results
VL only partially drives expression of cleaved caspase-3
(CC3). CC3hi HIV sp CTL in EC were not only lower com-
pared to V (2.3 vs. 13%, respectively) but also lower than
ST (5.4%) (p < 0.05). Bcl-2 trended towards higher levels
in HIV sp CTL of EC and ST compared to V. Combining
these makers we found differences in CC3hi/Bcl-2lo HIV sp
CTL with the greatest number of HIV sp CTL at risk of
apoptosis in viremics (6.5%), followed by ST (2.1%) and
EC (0.80%) (p < 0.05). In a longitudinal analysis pre and
post ART we found decreases in both CC3hi HIV sp CTL
and CC3hi/Bcl-2lo CTL after successful treatment. CC3hi/
Bcl-2lo populations represent cells at greatest risk of under-
going apoptosis and this phenotype appears to be only
partially reversible with ART.
Conclusion
EC have a survival advantage over patients with chronic
disease even when treated with ART. Elucidating pro- and
anti-apoptotic factors contributing to the survival of CTL
in EC including costimulatory signaling necessary to gen-
erate these CTL capable of resisting apoptosis is para-
mount to development of effective HIV-1 vaccines.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P254 doi:10.1186/1742-4690-6-S3-P254
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P254
© 2009 Heath et al; licensee BioMed Central Ltd. 


P16-25. HIV specific CTL from elite controllers have a unique survival advantage

P16-25. HIV specific CTL from elite controllers have a unique survival advantage

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